Pain represents a major health and economic problem throughout the world. Despite advances in understanding the physiological basis of pain, an ideal analgesic has yet to be discovered.
Among analgesic drugs, the opioid class of compounds is widely used for pain treatment. The opioid drugs produce effects by interacting with the opioid receptors. The existence of at least three opioid receptor types, μ (mu), δ (delta), and κ (kappa) has been established. All three opioid receptor types are located in the human central nervous system, and each has a role in the mediation of pain. Opioid receptors are also known to undergo heterodimerization when coexpressed in cultured cells. Among the reported opioid receptor heterodimers are delta/kappa, delta/mu, and kappa/mu. In cultured cells the effect of heterodimerization may be manifested in a number of ways, including changes in efficacy, function, trafficking, and ligand recognition.
Morphine and related opioids currently used as analgesics produce their analgesia primarily through their agonist action at mu opioid receptors. The administration of these drugs is limited by significant side effects such as the development of tolerance, physical dependence, addiction liability, constipation, respiratory depression, muscle rigidity, and emesis. Accordingly, there is a need for improved analgesics. In particular, there is a need for analgesics that are more potent than morphine or that produce fewer or reduced side-effects compared to existing analgesics.